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      Infections after T‐replete haploidentical transplantation and high‐dose cyclophosphamide as graft‐versus‐host disease prophylaxis

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          Abstract

          Background

          Recently, a platform of T‐cell replete haploidentical hematopoietic stem cell transplantation (haplo‐ HSCT) using post‐transplant cyclophosphamide (Cy) has shown high reproducibility and acceptable safety profile.

          Method

          This prospective cohort analysis allowed us to collect data on infections among 70 consecutive recipients of haplo‐ HSCT affected by various hematologic malignancies.

          Results

          After a median follow‐up of 23 months, cumulative incidence of viral infections was 70% (95% confidence interval [ CI] 59–81) at 100 days and 77% (95% CI 67–87) at 1 year; 35 of 65 patients at risk had CMV reactivation (54%) and the rate of polyomavirus‐virus‐associated cystitis was 19% (13/70). Cumulative incidence of bacterial and fungal infections at 1 year were 63% (95% CI 51–75) and 12% (95% CI 4–19), respectively. Of note, only 1 invasive fungal infection occurred beyond 1 year after transplant (day +739).

          Conclusion

          In conclusion, despite a high rate of viral infections in the early period, present data suggest a satisfactory infectious profile after T‐cell replete haplo‐ HSCT using post‐transplant Cy. These results may help clinicians to improve both prophylactic and therapeutic antimicrobial strategies in this emerging haploidentical setting.

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          Estimation of failure probabilities in the presence of competing risks: new representations of old estimators.

          T Gooley, W Leisenring, J. Crowley … (1999)
          A topic that has received attention in both the statistical and medical literature is the estimation of the probability of failure for endpoints that are subject to competing risks. Despite this, it is not uncommon to see the complement of the Kaplan-Meier estimate used in this setting and interpreted as the probability of failure. If one desires an estimate that can be interpreted in this way, however, the cumulative incidence estimate is the appropriate tool to use in such situations. We believe the more commonly seen representations of the Kaplan-Meier estimate and the cumulative incidence estimate do not lend themselves to easy explanation and understanding of this interpretation. We present, therefore, a representation of each estimate in a manner not ordinarily seen, each representation utilizing the concept of censored observations being 'redistributed to the right.' We feel these allow a more intuitive understanding of each estimate and therefore an appreciation of why the Kaplan-Meier method is inappropriate for estimation purposes in the presence of competing risks, while the cumulative incidence estimate is appropriate.
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            Reduced mortality after allogeneic hematopoietic-cell transplantation.

            Ted Gooley, Jason Chien, Steven A Pergam … (2010)
            Over the past decade, advances have been made in the care of patients undergoing transplantation. We conducted a study to determine whether these advances have improved the outcomes of transplantation. We analyzed overall mortality, mortality not preceded by relapse, recurrent malignant conditions, and the frequency and severity of major complications of transplantation, including graft-versus-host disease (GVHD) and hepatic, renal, pulmonary, and infectious complications, among 1418 patients who received their first allogeneic transplants at our center in Seattle in the period from 1993 through 1997 and among 1148 patients who received their first allogeneic transplants in the period from 2003 through 2007. Components of the Pretransplant Assessment of Mortality (PAM) score were used in regression models to adjust for the severity of illness at the time of transplantation. In the 2003-2007 period, as compared with the 1993-1997 period, we observed significant decreases in mortality not preceded by relapse, both at day 200 (by 60%) and overall (by 52%), the rate of relapse or progression of a malignant condition (by 21%), and overall mortality (by 41%), after adjustment for components of the PAM score. The results were similar when the analyses were limited to patients who received myeloablative conditioning therapy. We also found significant decreases in the risk of severe GVHD; disease caused by viral, bacterial, and fungal infections; and damage to the liver, kidneys, and lungs. We found a substantial reduction in the hazard of death related to allogeneic hematopoietic-cell transplantation, as well as increased long-term survival, over the past decade. Improved outcomes appear to be related to reductions in organ damage, infection, and severe acute GVHD. (Funded by the National Institutes of Health.).
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              Long-term survival and late deaths after allogeneic hematopoietic cell transplantation.

              John Wingard, Navneet S Majhail, Ruta Brazauskas … (2011)
              Allogeneic hematopoietic cell transplantation (HCT) is curative but is associated with life-threatening complications. Most deaths occur within the first 2 years after transplantation. In this report, we examine long-term survival in 2-year survivors in the largest cohort ever studied. Records of 10,632 patients worldwide reported to the Center for International Blood and Marrow Transplant Research who were alive and disease free 2 years after receiving a myeloablative allogeneic HCT before 2004 for acute myelogenous or lymphoblastic leukemia, myelodysplastic syndrome, lymphoma, or severe aplastic anemia were reviewed. Median follow-up was 9 years, and 3,788 patients had been observed for 10 or more years. The probability of being alive 10 years after HCT was 85%. The chief risk factors for late death included older age and chronic graft-versus-host disease (GVHD). For patients who underwent transplantation for malignancy, relapse was the most common cause of death. The greatest risk factor for late relapse was advanced disease at transplantation. Principal risk factors for nonrelapse deaths were older age and GVHD. When compared with age, sex, and nationality-matched general population, late deaths remained higher than expected for each disease, with the possible exception of lymphoma, although the relative risk generally receded over time. The prospect for long-term survival is excellent for 2-year survivors of allogeneic HCT. However, life expectancy remains lower than expected. Performance of HCT earlier in the course of disease, control of GVHD, enhancement of immune reconstitution, less toxic regimens, and prevention and early treatment of late complications are needed.
              Article 0 comments Cited 193 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Transpl Infect Dis
                Journal ID (iso-abbrev): Transpl Infect Dis
                Journal ID (doi): 10.1111/(ISSN)1399-3062
                Journal ID (publisher-id): TID
                Title: Transplant Infectious Disease
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1398-2273
                ISSN (Electronic): 1399-3062
                Publication date (Electronic): 26 March 2015
                Publication date (Print): April 2015
                Volume: 17
                Issue: 2 ( doiID: 10.1111/tid.2015.17.issue-2 )
                Pages: 242-249
                Affiliations
                [ 1 ] Department of Oncology and Hematology Humanitas Cancer Center Humanitas Clinical and Research Center Milan Italy
                [ 2 ] Molecular Biology Section Clinical Investigation Laboratory Humanitas Clinical and Research Center Milan Italy
                [ 3 ] Microbiology Section Clinical Investigation Laboratory Humanitas Clinical and Research Center Milan Italy
                [ 4 ] Infectious Disease Unit Humanitas Clinical and Research Center Milan Italy
                [ 5 ] Unit of Clinical and Experimental Immunology Humanitas Clinical and Research Center Milan Italy
                [ 6 ] Department of Medical Biotechnology and Translational Medicine University of Milano Milan Italy
                Author notes
                [*] [* ] Correspondence to:

                Roberto Crocchiolo, MD, PhD, Humanitas Cancer Center, Via Manzoni, 56, 20089 Rozzano (Milan), Italy

                Tel: +39‐0282247291

                Fax: +39‐0282248812

                E‐mail: roberto.crocchiolo@ 123456cancercenter.humanitas.it

                Article
                Publisher ID: TID12365
                DOI: 10.1111/tid.12365
                PMC ID: 7169814
                PubMed ID: 25648539
                SO-VID: b58df278-b380-4005-abfe-3f1b9ad5a3f3
                Copyright © © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
                License:

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                Date received : 23 September 2014
                Date revision received : 24 November 2014
                Date accepted : 18 January 2015
                Page count
                Pages: 8
                Categories
                Subject: Original Report
                Subject: Original Reports
                Custom metadata
                source-schema-version-number 2.0
                cover-date April 2015
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                ScienceOpen disciplines: Transplantation
                Keywords: infections,haploidentical stem cell transplantation,t‐cell replete,antimicrobial prophylaxis,hematologic malignancies,cyclophosphamide
                Data availability:
                ScienceOpen disciplines: Transplantation
                Keywords: infections, haploidentical stem cell transplantation, t‐cell replete, antimicrobial prophylaxis, hematologic malignancies, cyclophosphamide

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